Oral tributyrin prevents endotoxin-induced lipid metabolism disorder

Abstract

Sepsis leads to dysregulation of lipid and lipoprotein metabolism. Butyrate increases peroxisome proliferator-activated receptors (PPARs), which are key nuclear hormone receptors to induce fatty acid oxidation and synthesis. Oral administration of tributyrin, a prodrug of butyrate contained in dairy products, suppresses lipopolysaccharide (LPS)-induced liver injury through attenuating nuclear factor-κB activity with an increased hepatoportal butyrate level. In this study, we elucidated the protective effect of oral administration of tributyrin against LPS-mediated lipid metabolism disorder in rats. Male Wistar rats were randomly divided and were administered tributyrin or vehicle orally 1h before LPS injection and then sacrificed at 0, 1.5, 6, and 24h after LPS. Liver tissue expressions of nuclear hormone receptors, enzymes associated with fatty acid metabolism, and histone acetylation were analyzed by real-time polymerase chain reaction or western blotting. Plasma lipids levels were measured. Tributyrin enhanced expression of PPARs and histone H3 in the liver at basal levels. Tributyrin suppressed LPS-induced repression of PPARs fatty acid oxidation-associated enzymes: fatty acid transport protein and fatty acid binding protein, and fatty acid synthesis-associated enzyme: sterol regulatory element binding protein-1c. Tributyrin reduced the increase in plasma triglyceride, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels at 24h after LPS injection. Oral tributyrin administration prevented elevation of plasma triglyceride, TC, and LDL-C levels through improved fatty acid oxidation in endotoxemic rats.